加州理工学院Lior Pachter研究组报道了在单细胞分辨率下检测病毒序列可识别与宿主基因表达变化相关的新型病毒。相关论文于2025年4月22日发表在《自然—生物技术》杂志上。

研究组介绍了一种基于高度保守的RdRP蛋白的方法，可以准确快速地检测大量病毒序列和单细胞转录组学数据，可以检测超过100,000种RNA病毒。在单细胞分辨率下并行分析病毒存在和宿主基因表达，可以表征宿主病毒组，鉴定病毒的趋向性和宿主反应。该课题组人员将他们的方法应用于患有埃博拉病毒病的恒河猴外周血单个核细胞数据，并描述了以前未知的假定病毒主题。

此外，课题组研究人员能够根据猕猴基因表达准确预测病毒在单个细胞中的存在。

据了解，高通量测序方法在研究、农业和医疗保健领域的应用日益广泛，为具有成本效益的病毒多样性监测和病毒-疾病相关性研究提供了机会。然而，现有的识别测序数据中的病毒主题的方法依赖并仅限于参考基因组，不能通过细胞条形码跟踪来保持单细胞分辨率。

附：英文原文

Title: Detection of viral sequences at single-cell resolution identifies novel viruses associated with host gene expression changes

Author: Luebbert, Laura, Sullivan, Delaney K., Carilli, Maria, Eldjrn Hjrleifsson, Kristjn, Viloria Winnett, Alexander, Chari, Tara, Pachter, Lior

Issue&Volume: 2025-04-22

Abstract: The increasing use of high-throughput sequencing methods in research, agriculture and healthcare provides an opportunity for the cost-effective surveillance of viral diversity and investigation of virus–disease correlation. However, existing methods for identifying viruses in sequencing data rely on and are limited to reference genomes or cannot retain single-cell resolution through cell barcode tracking. We introduce a method that accurately and rapidly detects viral sequences in bulk and single-cell transcriptomics data based on the highly conserved RdRP protein, enabling the detection of over 100,000 RNA virus species. The analysis of viral presence and host gene expression in parallel at single-cell resolution allows for the characterization of host viromes and the identification of viral tropism and host responses. We apply our method to peripheral blood mononuclear cell data from rhesus macaques with Ebola virus disease and describe previously unknown putative viruses. Moreover, we are able to accurately predict viral presence in individual cells based on macaque gene expression.

DOI: 10.1038/s41587-025-02614-y

Source: https://www.nature.com/articles/s41587-025-02614-y